![]() ![]() The end resection step is performed by a multisubunit helicase-nuclease complex, such as RecBCD in Escherichia coli ( 2, 3) and AddAB in Bacillus subtilis ( 4, – 6). Subsequently, resolvase activity releases two intact DNA duplexes. The nucleoprotein filament will be used to perform homology search and strand invasion within a homologous DNA sequence. The initiating step of the repair mechanism consists of the resection of the DSB end to generate a 3′ single-stranded tail onto which a synaptic protein (e.g., RecA in bacteria, RAD51 in humans) is loaded to form a nucleoprotein filament. The involvement of DSB repair by HR in a range of fundamental cellular processes (e.g., chromosome integrity, replication, segregation, etc.) reveals that HR is conserved in all living organisms. Indeed, illegitimate recombination (IR) does not require an intact homologous sequence but as a consequence has reduced fidelity. ![]() In nonreplicating phases, such as late stationary phase or in spores (which contain a single copy of the chromosome), DSBs are more likely repaired by an illegitimate repair pathway. In intensively replicating cells (vegetative growth phase) or immediately after the passing of the replication fork, the sister chromatid can be used as an intact template. In bacteria, DSBs are for the most part processed through HR, which requires a homologous DNA template to carry out faithful repair of the damaged DNA duplex. The failure to repair DSBs can lead to cell death and, in the case of disrepair, can trigger large-scale chromosome rearrangements, favoring the generation of genetic diversity. DSBs also result from replication fork collapse during chromosomal replication ( 1). They are induced in cells by physical agents such as ionizing radiation or UV light, chemical agents, and natural products such as mitomycin C (MMC) or bleomycin. ![]() Homologous recombination (HR) is a crucial mechanism that repairs a variety of DNA lesions, including DNA double-strand breaks (DSBs), single-strand DNA gaps, and interstrand cross-links.ĭSBs are probably the most deleterious DNA damage that a cell can encounter. DNA damage needs to be repaired to avoid the formation of deleterious mutations, abortion of replication, and lethal chromosomal breakage. coli recB mutant restored viability and resistance to UV light, suggesting that Streptomyces AdnAB could be a functional homologue of RecBCD and be involved in DNA damage resistance.Ĭells are under constant genotoxic pressure from both endogenous and exogenous sources. Both adnA and adnB genes were shown to be inducible in response to DNA damage (mitomycin C) and to be independently transcribed. The disruption of adnAB in Streptomyces ambofaciens and Streptomyces coelicolor could not be achieved unless an ectopic copy was provided, indicating that adnAB is essential for growth. These genes are conserved as a single copy in all sequenced genomes of Streptomyces. The only putative helicase-nuclease-encoding genes identified were homologous to M. Here we show that in Streptomyces, neither recBCD nor addAB homologues could be detected. This multistep process is initiated by the resection of the broken DNA ends by a multisubunit helicase-nuclease complex exemplified by Escherichia coli RecBCD, Bacillus subtilis AddAB, and newly discovered Mycobacterium tuberculosis AdnAB. Homologous recombination is a crucial mechanism that repairs a wide range of DNA lesions, including the most deleterious ones, double-strand breaks (DSBs).
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